The Center for Computational Biology and Bioinformatics (C2B2) was established in 2003, with the mission of providing the biomedical research community with Structural and Systems Biology algorithms and software tools for the dissection of molecular interactions and for the interaction-based elucidation of cellular phenotypes. Over the last few years C2B2 investigators have developed many novel analysis methodologies which have led to important biological discoveries including understanding the role of DNA shape in protein- DNA binding specificity and the discovery of genes causally related to the presentation of malignant phenotypes, including Lymphoma, Glioma, and Melanoma. A common thread among all these computational investigations is their very significant computational requirements. This is a result of both the combinatorial nature of the algorithms as well as the genome-scale size of the data sets on which they are being applied. For example, more than 1 million CPU-hours were needed to generate the gene interaction network that was used to identify the master regulators that drive the mesenchymal phenotype in Glioma. In practical terms, such investigations are only feasible when carried out on a high performance computing (HPC) environment. To address this need, C2B2 has made significant investments in high performance IT infrastructure (utilizing grants from Columbia University, the New York State and the NIH) and has assembled one of the largest HPC facilities dedicated to biological investigation in the nation. The centerpiece of the C2B2 HPC infrastructure is Titan, a 3712 core cluster which was ranked by Top500.org as the 124th fastest computer in the world when the system debuted in 2008. This infrastructure has been instrumental to the success of C2B2, by enabling Center researchers to execute computational investigations that would have otherwise been infeasible and by allowing us to recruit and retain world class faculty. As has been the case in the past, we have now reached a point where the computational needs of our investigators are exceeding the limits of our HPC infrastructure. Historical utilization data demonstrate that computation consumption has been doubling annually. As a result, Titan has been running at its peak capacity for the past six to eight months. We anticipate that demand for computation will increase even further as C2B2 is in the process of transitioning from a Center to a full University Department (Dept. of Systems Biology) with approved budget for 9 more faculty hires. Through this application we seek to quadruple our computational capacity to accommodate the data analysis needs of several NIH funded projects over a period of 2-3 years. Given the central role of computing in the research program of C2B2, the availability of an adequate and easily accessible HPC environment is a critical prerequisite for the successful completion of these projects. The equipment purchase requested here will allow us to continue serving the needs of biomedical research at Columbia University for the foreseeable future.